DESCRIPTION (Adapted from the Abstract): Group A streptococci (S. pyogenes) produce many different extracellular products, which display a variety of tissue damaging and pharmacological activities. Several of these products have been suggested to play important roles in the pathogenesis of disease. However, the exact role of many of these products remains to be elucidated. This investigation focuses on one of these extracellular products, hyaluronidase, which has received relatively little attention in recent years. Hyaluronidase is one product which potentially has a significant role in the pathogenesis of group A streptococcal infections, by allowing the organism to spread from an initial site of infection. The Specific Aims of this proposal are: (1) Determination of the nucleotide sequence of the structural gene (hyl/A) encoding the active extracellular streptococcal hyaluronidase (2) Conduct an epidemiological analysis of the hyaluronidase gene (hyl/A) among group A streptococci, in particular those strains associated with streptococcal diseases. (3) Begin to ascertain the regulatory mechanisms for hyaluronidase gene expression, particularly the relationship between production of hyaluronidase and factors such as aeration and production of the hyaluronic acid capsule. The group A streptococcus is a complex organism, and an understanding of all its extracellular products and how these are produced is important in comprehending how streptococci are able to initiate the wide variety of diseases attributed to this pathogen. This study is meant to be an initial step in understanding the role of hyaluronidase in the pathogenesis of infections caused by S. pyogenes.